Water → 2-Bromo-1-(4-methoxy-3-morpholin-4-yl-5-trifluoromethylphenyl)ethanone

Temperature

7 °C

4-[5-(1,1-Dimethoxyethyl)-2-methoxy-3-trifluormethylphenyl]morpholine (O2.004; 460 mg) was dissolved in a mixture of methanol (1.4 ml) and THF (4 ml), the mixture was cooled to 7° C., and phenyltrimethylammonium tribromide (530 mg) was added in portions while stirring. After stirring at RT for 3 h, the mixture was left to stand overnight. Then aqueous thiosulfate solution (0.8 ml; w=5%) and water (4 ml) were added, and the mixture was admixed with EA and extracted three times with EA. The combined extracts were dried over magnesium sulfate, filtered and concentrated. The residue was dissolved in a mixture of acetonitrile (20 ml) and water (0.5 ml) and admixed with TFA (0.5 ml) while stirring. After stirring at RT for 5 h, the solvent was drawn off, and the residue was admixed with water, neutralized with saturated sodium hydrogencarbonate solution and extracted three times with ethyl acetate. The combined extracts were dried over magnesium, filtered and concentrated. The crude product was purified using silica gel with ethyl acetate/heptane as the eluent. 200 mg of the desired compound were obtained.

1. stirringAfter stirring at RT for 3 h
2. waitthe mixture was left
3. extractionextracted three times with EA
4. dry with materialThe combined extracts were dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in a mixture of acetonitrile (20 ml) and water (0.5 ml)
8. stirringwhile stirring
9. stirringAfter stirring at RT for 5 h
10. extractionextracted three times with ethyl acetate
11. dry with materialThe combined extracts were dried over magnesium
12. filtrationfiltered
13. concentrationconcentrated
14. customThe crude product was purified

ORD record

ord-76afa76523db41d3be3808aeb35c4758

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08198272B2